Pulmonary gas exchange requires the efficient distribution of inspired gas and pulmonary capillary blood within the respiratory zone of the lung. Postural alterations in anesthetized animals interfere with gas exchange resulting in reduced arterial oxygen tensions. Compromised ventilation with ensuing ventilation perfusion mismatching is a likely cause. Curiously, although implicated in several reports, no studies have directly determined the influence of the heart and mediastinum on lung function, which may contribute to the observed hypoxemia. We propose to utilize pneumonectomized rabbits to determine the influence of mediastinal structures on pulmonary ventilation and perfusion. Pneumonectomy with and without volume compensation in the remaining lung will provide known alterations in mediastinal position relative to the remaining lung. Comparison of pulmonary function studies quantifying lung volume and pulmonary ventilation and perfusion distribution, and pleural pressure in right and left lateral recumbency should indicate the effect of the mediastinum on lung function. In one position, the heart will be over the remaining lung and in the other, the remaining lung will be over the heart. The material properties of the lung will be measured to quantify the distensibility and distortability of the remaining lung relative to normal lung tissue. Changes in lung shape and density within the thorax will be quantified by CT scanning. Physiological studies of lung function will be compared with morphometically derived alveolar surface area to volume ratios. Finally, pulmonary function studies quantifying lung volume and ventilation distribution will be performed in humans in right and left lateral recumbency. Humans who have undergone therapeutic pneumonectomy will be studied and the results will be compared with the rabbit model. These studies should provide new information regarding the mechanical interaction between the heart and lungs and its effect on gas exchange efficiency.